GAP-43 is a neuronal specific, membrane-associated protein highly expressed in the hippocampus. It is important in neurite outgrowth, regeneration and plasticity. Its modulation has also been linked to LTP induction and persistence in the hippocampus. GAP-43 is a protein kinase C (PKC) substrate and as such may play an important role in learning and memory processes is well documented, the substrates PKC acts upon and the processes it alters for learning to occur have not been elucidated. The proposal is designed to explore the modulation of GAP-43 following contextual fear conditioning and correlate any changes in expression or phosphorylation with the degree of learning. Emphasis will be differences in GAP-43 levels and phosphorylationstate arising as a result of training. There is preliminary evidence for changes in GAP-43 protein levels. Such changes in the levels or phosphorylation state of GAP-43 may modulate hippocampal neurotransmitter release, potentially a mechanism for learning to occur. The proposed studies will be carried out using western blotting, phosphorylation assays and neurotransmitter release assays.